Ischemic Vascular Damage Can Be Repaired by Healthy, but Not Diabetic, Endothelial Progenitor Cells

Caballero, Sergio; Sengupta, Nilanjana; Afzal, Aqeela; Chang, Kyung Hee; Calzi, Sergio Li; Guberski, Dennis L.; Kern, Timothy S.; Grant, Maria B.

doi:10.2337/db06-1254

Cited by 242 publications

(237 citation statements)

References 50 publications

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“…By contrast, studies using animal models for ocular vascular damage, including diabetes, ischemia/reperfusion injury and OIR, have shown that cells from normal donors attach and assimilate into the existing vasculature. However, cells from diabetic donors uniformly were unable to integrate into damaged vasculature (Caballero et al, 2007). These findings further indicate that healthy EPCs can effectively repair injured retina and that there is defective repair of vasculature in patients with diabetes.…”

Section: Vegf and Retinalmentioning

confidence: 78%

Vascular endothelial growth factor in eye disease

Penn

Madan

Caldwell

et al. 2008

Progress in Retinal and Eye Research

636

527

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Collectively, angiogenic ocular conditions represent the leading cause of irreversible vision loss in developed countries. In the U.S., for example, retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration are the principal causes of blindness in the infant, working age and elderly populations, respectively. Evidence suggests that vascular endothelial growth factor (VEGF), a 40 kDa dimeric glycoprotein, promotes angiogenesis in each of these conditions, making it a highly significant therapeutic target. However, VEGF is pleiotropic, affecting a broad spectrum of endothelial, neuronal and glial behaviors, and confounding the validity of anti-VEGF strategies, particularly under chronic disease conditions. In fact, among other functions VEGF can influence cell proliferation, cell migration, proteolysis, cell survival and vessel permeability in a wide variety of biological contexts. This article will describe the roles played by VEGF in the pathogenesis of retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. The potential disadvantages of inhibiting VEGF will be discussed, as will the rationales for targeting other VEGF-related modulators of angiogenesis.

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Section: Vegf and Retinalmentioning

confidence: 78%

Vascular endothelial growth factor in eye disease

Penn

Madan

Caldwell

et al. 2008

Progress in Retinal and Eye Research

636

527

View full text Add to dashboard Cite

show abstract

“…The obese BBZDR/Wor rat is lymphopenic, hyperinsulinemic with peripheral insulin resistance and develops spontaneous autoimmune non-insulin-dependent diabetes mellitus at an age of 70 days (18). Results in the oxygen-induced retinopathy model and the STZ model using endothelial cell progenitor cells suggest that the BBZDR/Wor rat is a good model of type 2 diabetic retinal changes (17).…”

Section: Methodsmentioning

confidence: 99%

“…The BBZDR/Wor rat model of type 2 diabetes has been used for studies of autonomic neuropathy (14,15), myogenic tone of the ophthalmic artery (16), and vascular damage repair using endothelial cell progenitors (17). The BBZDR/Wor rat was produced using the BBZDP/Wor (BB rat with an Iddm2 type 1 genetic locus) and mating with lean BBZ/Wor rats (BB rat with Zucker diabetic gene) to remove the Iddm2 locus.…”

Section: Methodsmentioning

confidence: 99%

Pioglitazone Normalizes Insulin Signaling in the Diabetic Rat Retina through Reduction in Tumor Necrosis Factor α and Suppressor of Cytokine Signaling 3

Jiang

Thakur

Bheemreddy

et al. 2014

Journal of Biological Chemistry

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“…Furthermore, Werner and colleagues reported both a step-wise increase in cumulative event-free survival of life-threatening cardiovascular incidents with increasing baseline levels of CD34+VEGFR-2+ EPCs, and an association between CD133+ cell counts and reduced occurrence of a first major cardiovascular event and hospitalisation [24]. Circulating EPCs in people with diabetes are not only reduced in number, but also have impaired function [25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Circulating endothelial progenitor cells, endothelial function, carotid intima–media thickness and circulating markers of endothelial dysfunction in people with type 1 diabetes without macrovascular disease or microalbuminuria

et al. 2009

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Aims/hypothesis Type 1 diabetes is associated with premature arterial disease. Bone-marrow derived, circulating endothelial progenitor cells (EPCs) are believed to contribute to endothelial repair. The hypothesis tested was that circulating EPCs are reduced in young people with type 1 diabetes without vascular injury and that this is associated with impaired endothelial function and increased carotid intima-media thickness (CIMT). Methods We compared 74 people with type 1 diabetes with 80 healthy controls. CD34, CD133, vascular endothelial (VE) growth factor receptor-2 (VEGFR-2) and VE-cadherin antibodies were used to quantify EPCs and progenitor cell subtypes using flow-cytometry. Ultrasound assessment of endothelial function by brachial artery flow-mediated dilatation (FMD) and CIMT was made. Circulating endothelial markers, inflammatory markers and plasma plasminogen activator inhibitor-1 (PAI-1) levels were measured. Results CD34+VE-cadherin+, CD133+VE-cadherin+ and CD133+VEGFR-2+ EPC counts were significantly lower in people with diabetes (46-69%; p=0.004-0.043). In people with type 1 diabetes, FMD was reduced by 45% (p<0.001) and CIMT increased by 25% (p<0.001), these being correlated (r=−0.25, p=0.033). There was a significant relationship between FMD and CD34+VE-cadherin+ (r = 0.39, p = 0.001), CD133+VEGFR-2+ (r =0.25, p = 0.037) and CD34+ (r=0.34, p=0.003) counts. Circulating high-sensitivity C-reactive protein, PAI-1, interleukin-6 and E-selectin were significantly higher in the diabetes group (p < 0.001 to p = 0.049), the last two of these correlating with FMD (r=−0.27, p=0.028 and r=−0.24, p=0.048, respectively). Conclusions/interpretation These findings suggest that abnormalities of endothelial function in addition to proinflammatory and pro-thrombotic states are already common in people with type 1 diabetes before development of clinically evident arterial damage. Low EPC counts confirm risk of macrovascular complications and may account for impaired endothelial function and predict future cardiovascular events.

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Ischemic Vascular Damage Can Be Repaired by Healthy, but Not Diabetic, Endothelial Progenitor Cells

Abstract: Endothelial precursor cells (EPCs

Cited by 242 publications

References 50 publications

Vascular endothelial growth factor in eye disease

Vascular endothelial growth factor in eye disease

Pioglitazone Normalizes Insulin Signaling in the Diabetic Rat Retina through Reduction in Tumor Necrosis Factor α and Suppressor of Cytokine Signaling 3

Circulating endothelial progenitor cells, endothelial function, carotid intima–media thickness and circulating markers of endothelial dysfunction in people with type 1 diabetes without macrovascular disease or microalbuminuria

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